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Li Y, Qiu Q, Fan Z, He P, Chen H, Jiao X. Th17 cytokine profiling of colorectal cancer patients with or without enterovirus 71 antigen expression. Cytokine 2018; 107:35-42. [PMID: 29175261 DOI: 10.1016/j.cyto.2017.11.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/05/2017] [Accepted: 11/17/2017] [Indexed: 02/07/2023]
Abstract
OBJECT Th17 cytokines have been identified in several types of human cancers. In this pilot study, the expression of Th17 cytokines profiling in enteroviruses 71 (EV71) associated colorectal cancer (CRC) were explored. METHODS 66 patients with CRC were enrolled in this study; immune- histochemical analyses were performed on cancerous tissues and adjacent non- cancerous tissues of the patients. Serum Th17 cytokines of CRC patients and healthy controls were measured using a Luminex 200 analyzer. RESULTS Cancerous tissues had more positive EV71 antigen expression than adjacent non- cancerous tissues. In TNM II-III CRC, 59.9% of cancerous tissues were observed to be EV71 positive; on the contrary, 65.2% of the adjacent non- cancerous epithelium was EV71 negative. In TNM I CRC, all adjacent non- cancerous epithelium was virus negative, but in TNM IV, half of adjacent non- cancerous tissues were virus positive. Serum IL-10 were significantly higher in CRC patients than in healthy controls, and IL-10 concentrations in the EV71 positive group were higher than those of the EV71 negative group, with the highest IL-10 levels being observed in CRC patients with strong positive group (P < 0.05). Similar results were found for IL-21 and IL-23. IL-17 levels were higher in CRC patients than in healthy controls, there was no significant difference in IL-17 between the viral positive and viral negative groups (P > 0.05). CONCLUSION Persistent existing EV71 viral antigens in intestinal tissues are positively associated with TNM III/IV CRC. EV71 latent infection recruits Th17 cells in the colorectal tumor site, stimulating Th17 cytokine production that closely associated with CRC carcinogenesis.
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Affiliation(s)
- Yazhen Li
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, China.
| | - Qiancheng Qiu
- The first affiliated hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China.
| | - Zhiqiang Fan
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, China.
| | - Ping He
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, China.
| | - Huanzhu Chen
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, China.
| | - Xiaoyang Jiao
- Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, China.
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Volpi CC, Gualeni AV, Pietrantonio F, Vaccher E, Carbone A, Gloghini A. Bright-field in situ hybridization detects gene alterations and viral infections useful for personalized management of cancer patients. Expert Rev Mol Diagn 2018; 18:259-277. [PMID: 29431533 DOI: 10.1080/14737159.2018.1440210] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
INTRODUCTION Bright-field in situ hybridization (ISH) methods detect gene alterations that may improve diagnostic precision and personalized management of cancer patients. Areas covered: This review focuses on some bright-field ISH techniques for detection of gene amplification or viral infection that have already been introduced in tumor pathology, research and diagnostic practice. Other emerging ISH methods, for the detection of translocation, mRNA and microRNA have recently been developed and need both an optimization and analytical validation. The review also deals with their clinical applications and implications on the management of cancer patients. Expert commentary: The technology of bright-field ISH applications has advanced significantly in the last decade. For example, an automated dual-color assay was developed as a clinical test for selecting cancer patients that are candidates for personalized therapy. Recently an emerging bright-field gene-protein assay has been developed. This method simultaneously detects the protein, gene and centromeric targets in the context of tissue morphology, and might be useful in assessing the HER2 status particularly in equivocal cases or samples with heterogeneous tumors. The application of bright-field ISH methods has become the gold standard for the detection of tumor-associated viral infection as diagnostic or prognostic factors.
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Affiliation(s)
- Chiara C Volpi
- a Department of Pathology and Laboratory Medicine , Fondazione IRCCS, Istituto Nazionale dei Tumori , Milano , Italy
| | - Ambra V Gualeni
- a Department of Pathology and Laboratory Medicine , Fondazione IRCCS, Istituto Nazionale dei Tumori , Milano , Italy
| | - Filippo Pietrantonio
- b Department of Medical Oncology , Fondazione IRCCS, Istituto Nazionale dei Tumori , Milano , Italy
| | - Emanuela Vaccher
- c Department of Medical Oncology , Centro di Riferimento Oncologico, IRCCS, National Cancer Institute , Aviano , Italy
| | - Antonino Carbone
- d Department of Pathology , Centro di Riferimento Oncologico, IRCCS, National Cancer Institute , Aviano , Italy
| | - Annunziata Gloghini
- a Department of Pathology and Laboratory Medicine , Fondazione IRCCS, Istituto Nazionale dei Tumori , Milano , Italy
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Mañon R, Schimp V, Gopalan P, Pattani K, Tseng J. The Impact of HPV as an Etiological Factor in Gynecological and Oropharyngeal Cancer. Am J Lifestyle Med 2016; 10:253-261. [PMID: 30202280 PMCID: PMC6125059 DOI: 10.1177/1559827615569707] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Revised: 11/02/2014] [Accepted: 11/05/2014] [Indexed: 12/15/2022] Open
Abstract
The human papilloma virus (HPV) is one of several viral pathogens linked to human cancer. This article reviews the current worldwide cancer burden related to this pathogen. The article also examines the role of HPV in oropharyngeal and gynecological malignancies, current treatment implications, and future directions in the treatment and prevention of HPV-related disease.
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Affiliation(s)
- Rafael Mañon
- Rafael Mañon, MD, Department of Radiation Oncology, UF Health Cancer Center, Orlando Health, 1400 S Orange Ave, MP 760, Orlando, FL 32806; e-mail:
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De Paoli P, Carbone A. Microenvironmental abnormalities induced by viral cooperation: Impact on lymphomagenesis. Semin Cancer Biol 2015; 34:70-80. [DOI: 10.1016/j.semcancer.2015.03.009] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 02/10/2015] [Accepted: 03/19/2015] [Indexed: 01/01/2023]
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Carbone A, Vaccher E, Gloghini A, Pantanowitz L, Abayomi A, de Paoli P, Franceschi S. Diagnosis and management of lymphomas and other cancers in HIV-infected patients. Nat Rev Clin Oncol 2014; 11:223-38. [PMID: 24614140 DOI: 10.1038/nrclinonc.2014.31] [Citation(s) in RCA: 92] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Despite the introduction of highly active antiretroviral therapy or combination antiretroviral therapy (HAART and cART, respectively) patients infected with HIV might develop certain types of cancer more frequently than uninfected people. Lymphomas represent the most frequent malignancy among patients with HIV. Other cancer types that have increased in these patients include Kaposi sarcoma, cancer of the cervix, anus, lung and liver. In the post-HAART era, however, patients with HIV have experienced a significant improvement in their morbidity, mortality and life expectancy. This Review focuses on the different types of lymphomas that generally occur in patients with HIV. The combination of cART and antineoplastic treatment has resulted in remarkable prolongation of disease-free survival and overall survival among patients with HIV who develop lymphoma. However, the survival in these patients still lags behind that of patients with lymphoma who are not infected with HIV. We also provide an update of epidemiological data, diagnostic issues, and strategies regarding the most-appropriate management of patients with both HIV and lymphomas.
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Affiliation(s)
- Antonino Carbone
- Department of Pathology, Centro di Riferimento Oncologico Aviano (CRO), Istituto Nazionale Tumori, Italy
| | - Emanuela Vaccher
- Department of Medical Oncology, Centro di Riferimento Oncologico Aviano (CRO), Istituto Nazionale Tumori, Italy
| | - Annunziata Gloghini
- Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Italy
| | - Liron Pantanowitz
- Department of Pathology, University of Pittsburgh Medical Center, USA
| | - Akin Abayomi
- Department of Pathology, Division of Haematology, Tygerberg Hospital, South Africa
| | - Paolo de Paoli
- Molecular Virology and Scientific Directorate, Centro di Riferimento Oncologico Aviano (CRO), Istituto Nazionale Tumori, Italy
| | - Silvia Franceschi
- Infections and Cancer Epidemiology Group, International Agency for Research on Cancer, France
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Schadler KL, Crosby EJ, Zhou AY, Bhang DH, Braunstein L, Baek KH, Crawford D, Crawford A, Angelosanto J, Wherry EJ, Ryeom S. Immunosurveillance by antiangiogenesis: tumor growth arrest by T cell-derived thrombospondin-1. Cancer Res 2014; 74:2171-81. [PMID: 24590059 DOI: 10.1158/0008-5472.can-13-0094] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Recent advances in cancer immunotherapy suggest that manipulation of the immune system to enhance the antitumor response may be a highly effective treatment modality. One understudied aspect of immunosurveillance is antiangiogenic surveillance, the regulation of tumor angiogenesis by the immune system, independent of tumor cell lysis. CD4(+) T cells can negatively regulate angiogenesis by secreting antiangiogenic factors such as thrombospondin-1 (TSP-1). In tumor-bearing mice, we show that a Th1-directed viral infection that triggers upregulation of TSP-1 in CD4(+) and CD8(+) T cells can inhibit tumor angiogenesis and suppress tumor growth. Using bone marrow chimeras and adoptive T-cell transfers, we demonstrated that TSP-1 expression in the T-cell compartment was necessary and sufficient to inhibit tumor growth by suppressing tumor angiogenesis after the viral infection. Our results establish that tumorigenesis can be stanched by antiangiogenic surveillance triggered by an acute viral infection, suggesting novel immunologic approaches to achieve antiangiogenic therapy.
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Affiliation(s)
- Keri L Schadler
- Authors' Affiliations: Department of Cancer Biology, Abramson Family Cancer Research Institute; Department of Microbiology, Institute for Immunology, Perelman School of Medicine; Department of Pathobiology, Veterinary School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Children's Hospital, Boston, Massachusetts; and Department of Molecular and Cellular Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, South Korea
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Carbone A, Gloghini A. Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment. World J Gastroenterol 2013; 19:7874-7879. [PMID: 24307781 PMCID: PMC3848135 DOI: 10.3748/wjg.v19.i44.7874] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 10/31/2013] [Accepted: 11/13/2013] [Indexed: 02/06/2023] Open
Abstract
The relationships between lymphomas and their microenvironment appear to follow 3 major patterns: (1) an independent pattern; (2) a dependent pattern on deregulated interactions; and (3) a dependent pattern on regulated coexistence. Typical examples of the third pattern are hepatitis C virus (HCV)-associated marginal zone lymphomas (MZLs) and mucosa-associated lymphoid tissue lymphomas. In these lymphomas, a regulated coexistence of the malignant cells and the microenvironmental factors usually occurs. At least initially, however, tumor development and cell growth largely depend on external signals from the microenvironment, such as viral antigens, cytokines, and cell-cell interactions. The association between HCV infection and B-cell lymphomas is not completely defined, although this association has been demonstrated by epidemiological studies. MZL and diffuse large B-cell lymphoma are the histotypes most frequently associated with HCV infection. Many mechanisms have been proposed for explaining HCV-induced lymphomagenesis; antigenic stimulation by HCV seems to be fundamental in establishing B-cell expansion as observed in mixed cryoglobulinemia and in B-cell lymphomas. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-associated indolent lymphomas. Importantly, clinically responses were linked to the eradication of the HCV-RNA, providing a strong argument in favor of a causative link between HCV and lymphoproliferation.
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MESH Headings
- Animals
- Cell Proliferation
- Hepacivirus/immunology
- Hepacivirus/pathogenicity
- Hepatitis C/complications
- Hepatitis C/immunology
- Humans
- Inflammation Mediators/metabolism
- Lymphangiogenesis
- Lymphoma, B-Cell, Marginal Zone/immunology
- Lymphoma, B-Cell, Marginal Zone/pathology
- Lymphoma, B-Cell, Marginal Zone/virology
- Lymphoma, Large B-Cell, Diffuse/immunology
- Lymphoma, Large B-Cell, Diffuse/pathology
- Lymphoma, Large B-Cell, Diffuse/virology
- Risk Factors
- Signal Transduction
- Tumor Microenvironment
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De Paoli P, Carbone A. Carcinogenic viruses and solid cancers without sufficient evidence of causal association. Int J Cancer 2013; 133:1517-29. [PMID: 23280523 DOI: 10.1002/ijc.27995] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2012] [Accepted: 12/07/2012] [Indexed: 01/01/2023]
Abstract
Viral infections are important risk factors for tumor development in humans. Selected types of cancers, either lymphomas or carcinomas, for which there is sufficient evidence in humans of a causal association with specific viruses, have been identified. Experimental and clinical data on the possible association of other tumor types and carcinogenic viruses are presently controversial. In this article, we review the current evidence on the relationship between breast, colorectal and lung cancers and carcinogenic viruses. The majority of the publications reviewed do not provide definitive evidence that the viruses studied are associated with breast, colon and lung cancers. However, since this association may be clinically relevant for some tumor subtypes (i.e., lung cancer and papillomaviruses), there is an urgent need for further investigation on this topic. Using innovative laboratory techniques for viral detection on well-defined tumor types, National and International networks against cancer should encourage and organize concerted research programs on viruses and solid cancer association.
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Affiliation(s)
- Paolo De Paoli
- Scientific Directorate, Centro di Riferimento Oncologico, IRCCS, Istituto Nazionale Tumori, Via Franco Gallini 2, Aviano, Italy.
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